The protozoan parasite Toxoplasma gondii commonly infects humans and poses an important threat to immunocompromised patients, primarily due to the potential for reactivation of latent infection. Our previous studies have shown that Toxoplasma gondii consists of three wide-spread clonal lineages and that the majority of human cases of toxoplasmosis (greater than 80 percent) are caused by type II strains. These findings imply that the small number of genetic differences between Toxoplasma strains underlie important biological differences, including their capacity to cause disease. The mechanisms of tissue pathology that occur during acute toxoplasmosis or reactivation of latency by different strains of Toxoplasma are poorly understood. To address this deficiency, we will examine the role of the parasite genotype in infection, dissemination, and tissue pathology during toxoplasmosis in the mouse model. We will identify and evaluate specific parasite genes that are responsible for pathology during toxoplasmosis focusing on genes that mediate acute virulence and genes that are associated with elevated levels of chronic infection. A combination of molecular genetic strategies will be used to directly test the role of specific parasite genes in toxoplasmosis in the mouse model. Identification of parasite virulence genes may facilitate future studies designed to combat toxoplasmosis in humans, including AIDS patients suffering from reactivation.